Implantable fibers and medical articles

ABSTRACT

An implantable medical article as well as an implantable fiber which is particularly useful for medical implants is disclosed. The fiber includes comprises a first component formed from a substantially resorbable material and a second component formed from a fiber-forming polymer.

RELATED APPLICATIONS

This application is a divisional of U.S. Application Ser. No.08/995,039, filed Oct. 31, 1997, now U.S. Pat. No. 6,162,537, whichclaims the benefit of U.S. Provisional Application No. 60/030,577, filedNov. 12, 1996. The entire teachings of the above applications areincorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to the field of fibers for usein medical implants and similar in vivo applications. More specifically,the invention relates to fibers for such applications including a firstcomponent formed from a resorbable material and a second componentformed from a fiber-forming polymer.

BACKGROUND OF THE INVENTION

The practice of medicine and the technology surrounding it continue toevolve in a dramatic fashion. One manifestation of this evolution is theincrease in the average human life span which alone spawns the need forstill further development, particularly in the area of implantablemedical articles, such as in the area of prostheses which either replaceor support failing, diseased or deteriorated anatomical parts.

Synthetic materials are known to be useful in the manufacture of many ofthese implantable articles. Among the more useful synthetic materials inthis application are fibers formed from synthetic polymers which aresubstantially non-resorbable and resistant to degradation in the body.These are often highly desirable for many implantable articleapplications because of their mechanical properties such as tensilestrength, flexibility, and elasticity. Furthermore, their ability to beengineered into useful structures and retain these mechanical propertiesunder the conditions present in the human body can be desirable. Forexample, certain synthetic fibers formed from polyester have been usedin the manufacture of vascular grafts, exhibiting sufficient strength towithstand the pressure of arterial or venous flow while also exhibitingflexibility and recovery. Additionally, fabric vascular grafts possessthe versatility to be conveniently implanted into the body withoutlosing structural strength.

For many applications of synthetic polymer fibers in the body, however,the fibers that retain suitable mechanical properties (such aspolyethylene terephthalate and polypropylene) do not provide the desiredbiologic response. Articles formed of these synthetic fibers often havethe risk of a negative reaction, for example, chronic inflammation,thrombosis and intimal hyperplasia, sometimes with potentially fatalresults.

Fibers made from polymers that can be resorbed by the body (often called“resorbable polymers”) can provide a positive and desired biologicresponse in the body. Examples of such resorbable polymers arepolyglycolic acid and polylactic acid and copolymers of glycolic withlactic acid or ε-caprolactone or trimethylene carbonate. In addition tothese polyesters are the polyester-ethers such as poly-p-dioxanone.

However, because these polymers are resorbable, the fibers made fromthem and implanted in the human body typically lose their mechanicalproperties in a time period considerably shorter than the needed life ofan implant. These materials are more typically used as a scaffold forthe growth and organization of implanted organ cells. Parenchymal cellsare isolated from the desired tissues and seeded into the polymer, andthe cell-polymer structure is implanted. While the scaffold graduallydeteriorates, the implanted cells proliferate and secrete substancesthat form an extracellular matrix (ECM). The growing cells, ECM, andvascular tissue continually replace the void spaces of the disappearingscaffold until eventually the implant has been replaced by naturaltissue. A spectacular example of this approach is an artificial—butliving—human external ear formed on a polymer matrix implantedsubcutaneously on the back of a laboratory animal. However, thisapproach may not be suitable for replacement of tissues that are subjectto continuous physical/mechanical demands, such as heart and bloodvessel walls, fasciae, ligaments and tendons, bursae and other jointtissues. Therefore, these fibers alone may not be optimal for use inimplant applications.

Thus a major problem is inherently present in implantable prostheticarticles that are formed from materials such as synthetic fibers becauseof the prior art fibers' inability to both retain good long termmechanical properties and also elicit a positive and desirable biologicresponse. One particular area in which this combination of desiredproperties has not been achieved is in the use of small bore (˜<6 mmdiameter) vascular grafts. Availability of suitable small diametervascular grafts could significantly expand the opportunities forvascular repair since arteries having diameters in this range, such asthe radial artery and the arteries in the Circle of Willis, provide amajor component of the blood supply to key organs and extremities andare often in need of repair due to injury or disease.

It is also known from Poiseuille's Law that flow through blood vesselsis proportional to the fourth power of the vessel radius. Reducing thediameter of a blood vessel by half, as may occur in intimal hyperplasiaor partial thrombosis, reduces the vessel's blood flow to {fraction(1/16)}th the original flow. Due to the small size and, in general, lowblood flow, these small grafts put an even greater demand on maintaininga clear cross-sectional area for blood flow. Unfortunately, there arecurrently no synthetic vascular grafts that work well in thisapplication. This is a severe problem and one for which a truly workablefiber and vascular graft fabric would be a major step forward.

Prior attempts to provide fibers with both long term mechanicalproperties and biocompatibility have been largely unsuccessful. Oneapproach has been to use resorbable fibers and biologically stablefibers such as those described above together in an implantable fabricsuch as a vascular graft. This approach is described, for example, inEPO Application 0 202 444 (Nov. 26, 1986) and U.S. Pat. No. 4,997,440(Mar. 5, 1991).

However, published results have shown that these types of constructionsfail because even a modest amount (20%) of the non-resorbable polymerfibers exposed and present inside the body (in this case polyethyleneterephthalate) significantly inhibited the desired biologic response (J.Vasc. Surgery, 3(5), May 1986). Furthermore, experimental resultsindicate that even at nominal levels of the non-resorbable component,problems of fabric failure and/or defects leading to potential aneurysmstill exist as indicated in U.S. Pat. No. 4,997,440 which indicates from“slight” to “significant” aneurysmal tendency in grafts with 25% to 33%non-resorbable fiber.

Another approach to address these limitations has been to coat theprosthetic fabric. For example, EPO Application 334 046 discloses asurgical composite which is manufactured by extruding a non-resorbablepolymer into a fiber, fabricating the fiber into a textile structure andthen encapsulating the structure with a resorbable polymer. Such anapproach has several drawbacks including changing the relativeflexibility of the basic fabric graft. Additionally, by virtue of thecoating process, the resulting fabric is less likely to have the smallopen pores and interstitial channels which are useful for cell andtissue ingrowth from outside the graft through the wall into the vessellumen. Further, such coating processes do not reliably provide adesirable uniform coating layer on individual filaments with controlledthickness of the coating layer.

A continuing need therefore still exists for a practical andeconomically manufacturable, useable implantable prosthetic articlewhich exhibits the properties necessary to perform the desired functionfor the prosthetic within the body while maintaining its structural andfunctional integrity and performance and bringing about a positivebiologic response leading to healing and the desired functioning of theprosthesis.

SUMMARY OF THE INVENTION

The present invention meets this need and also achieves the otherdesirable results discussed below by providing an implantable medicalarticle (for example, sterile medical articles) as well as animplantable fiber which is particularly useful for medical implants.

The fiber of this invention comprises a first component formed from asubstantially resorbable material and a second component formed from afiber-forming polymer.

In particular, a bicomponent fiber of the invention comprises a firstpolymer component formed from a substantially resorbable material and asecond component formed from a fiber-forming polymer wherein the volumeratio of said first component and second component is substantially thesame along the length of the fiber. In another embodiment, thebicomponent fiber of the invention comprises a first component formedfrom a substantially resorbable material and a second component formedfrom a fiber-forming polymer wherein the melting point of the secondcomponent is substantially the same as or less than the melting point ofthe first component. In a third embodiment of the invention, thebicomponent fiber comprises a first component formed from asubstantially resorbable material and a second component formed from afiber-forming polymer wherein said first component is substantially freeof cracks or delamination. The invention also includes bicomponentfibers comprising a first component formed from a substantiallyresorbable material and a second component formed from a fiber-formingpolymer wherein said first component possesses a substantially uniformthickness along the axis of the fiber. In yet another embodiment, thefiber is characterized by a first polymer component formed from asubstantially resorbable material and a second polymer componentmanufactured from a fiber-forming polymer wherein both the first andsecond components are substantially oriented. In a preferred embodiment,the bicomponent fiber is characterized by a first substantiallyresorbable component and second fiber-forming polymer component whereinsaid first and second component both contribute to the tenacity of thebicomponent fiber. In a preferred embodiment the bicomponent fibercontains two or more (including all) of the above describedcharacteristics in any combination. In a more preferred embodiment thefibers, as are described herein, are characterized by said secondcomponent being substantially disposed within said first component, asin a sheath/core configuration. Alternatively, the two components of thefiber are configured adjacent and parallel to each other along thelength of the fiber.

The invention also includes methods of manufacturing bicomponent fibers,particularly by solution wet spinning, melt spinning and solution dryspinning processes, as well as methods of using the bicomponent fibers,for example, in the manufacture of implantable fabrics (such as,knitted, braided and woven fabrics comprising one or more of thebicomponent fibers) and prosthetic devices and methods of using thebicomponent fibers and implantable fabrics made therefrom in vivo.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, features and advantages of theinvention will be apparent from the following more particulardescription of preferred embodiments of the invention, as illustrated inthe accompanying drawings in which like reference characters refer tothe same parts throughout the different views. The drawings are notnecessarily to scale, emphasis instead being placed upon illustratingthe principles of the invention.

The foregoing and other objects, features and advantages of theinvention will be apparent from the following more particulardescription of preferred embodiments of the invention, as illustrated inthe accompanying drawings in which like reference characters refer tothe same parts throughout the different views. The drawings are notnecessarily to scale, emphasis instead being placed upon illustratingthe principles of the invention.

FIGS. 1A, 1B and 1C are elevated cross-sectional views of separateembodiments of the present implantable fiber.

FIG. 2 is a schematic illustration of melt spinning process for formingthe fibers with an exploded cross-sectional view of a singular fiber.

FIG. 3 is a schematic illustration of a solution dry spinning processfor forming the present fibers with an exploded cross-sectional view ofa singular fiber.

FIG. 4 is a schematic illustration of a solution wet spinning formationprocess with a wet jet for forming the present fibers with an explodedcross-sectional view of a singular fiber.

FIG. 5 is a schematic illustration of a solution wet spinning formationprocess with a dry jet for forming the present fibers with an explodedcross-sectional view of a singular fiber.

FIG. 6 is an elevational view, partially in cross-section, of animplantable article of the present invention, more particularly avascular graft.

FIG. 7A is a top view of a portion of an embodiment of a textile basedstructure useful in the implantable article of the present invention.

FIG. 7B is a partially exploded portion of FIG. 7A.

FIGS. 8 and 9 are schematics of the draw equipment which can be used inthe manufacture of spun and drawn fibers.

DETAILED DESCRIPTION OF THE INVENTION

The term “fiber”, as utilized herein, is defined to include continuousfilaments, staple fibers formed therefrom and monofilament ormultifilament fibers.

As utilized herein, “bicomponent fibers” are fibers formed from 2 ormore components, each of which is distinct and discemable, i.e. notblended together.

The term “yarn” as utilized herein, is defined as a strand of fibers andcan be made from one or more bicomponent fibers (which can be the sameor different) of the invention, optionally, in combination with one ormore other fibers (e.g., not bicomponent fibers as described herein).

The term “polymer”, as utilized herein, is defined to includehomopolymers, copolymers, terpolymers and the like as well as polymerblends.

The term “biopositive”, as utilized herein, is defined as having thecapability, or property, of allowing and/or eliciting a positivebiologic response in the human body over time. Examples of positivebiologic responses include (but are not limited to) desirable growthfactor and cytokine stimulation, cellular migration and proliferationand tissue regeneration. It would be understood by one of ordinary skillin the art that whether or not a certain biologic response is positivemay depend on a number of factors, including, for example, theparticular application or desired function of the implantable article orimplantable fiber. In the case of an implantable fabric, such as anarterial graft, a biopositive polymer can be a polymer which, whenemployed as the sheath of a bicomponent fiber, will degrade in vivo overtime, the polymer or degradation products thereof, stimulating cellularmigration and/or tissue generation from outside the fabric or graftthrough the fabric or graft and into the vessel lumen. Tissue ingrowthcan be promoted by enhanced porosity produced by the resorption of thecomponent(s) of the bicomponent fiber. The biopositivity of the fiber orcomponent thereof can be imparted by the nature of the component or canbe imparted by the presence of an additive to the component, as will bedescribed in more detail below.

The term “resorbable material” as utilized herein, is defined as amaterial which is capable of being disassembled from its originalmolecular form by the human body and optionally eliminated from thehuman body by one or more mechanisms within the human body (for example,typically within one year of implantation). Polyglycolide polymers, suchas polyglycolic acid (PGA) and polylactide/polyglycolide copolymers(PLGA), for example, are hydrolyzed in vivo into soluble monomers and/orsoluble oligomers and, thus, eliminated.

FIGS. 1A, 1B and 1C illustrate cross-sections of two embodiments of theimplantable fiber 2 of the present invention. The fiber in FIG. 1A has afirst component 4 and a second component 6. The first component isformed from a substantially resorbable material. The second component ofthe fibers of the present invention is preferably substantially disposedwithin the first component. As illustrated, the second component issubstantially concentrically disposed within the first component. Thus,the second component can also be disposed in a non-concentricorientation. FIG. 1B illustrates a bicomponent fiber comprising a firstcomponent 4 formed from a substantially resorbable material and twosecond components (which can be the same or different) 6 which aredisposed within the first component. FIG. 1C illustrates a bicomponentfiber wherein the first and second component are each exposed to theexterior of the fiber. It will be understood by one of ordinary skill inthe art that the specific disposition of the two components will dependon a variety of factors, including for example the application/utilityof the fiber.

In general, the ratio of the first component to the second component maybe substantially the same for all fibers in an article which includessuch fibers. However, there may be some applications in which one woulddesire to have some fibers with a relatively thinner first componentwhich could be resorbed by the body in a relatively short time periodand other fibers with a relatively thicker first component which couldbe resorbed over a relatively longer time period.

The choice of the volume ratio of first component to second componentwill, in general, range from about 1:10 to about 10:1 with the specificchoice depending upon the particular fiber application. More preferablythe volume ratio of the first component to second component will varyfrom about 1:3 to about 3:1. Such control of the ratio of firstcomponent to second component for each and every fiber is within thescope and capability of the spinning techniques described in thisinvention and known in the art. Preferably, the ratio of the firstcomponent to the second component is substantially constant along thelength of the fiber.

The volume ratio of the components of the fiber can be calculated bydetermining the surface area of each component in a cross-section of thefiber and dividing the value obtained from the first component by thevalue obtained by the second component. By “substantially the same”, itis meant that at least about 90% (preferably at least about 95% and morepreferably at least about 99%) of a statistically significant number ofvolume ratios taken across the length of the fiber (e.g. a meter ormore) vary in an amount less than 10%. It is particularly preferred thatthe first component (or the sheath of the fiber) be substantially freeof cracking or delamination.

Similarly, the geometric distribution of the second and first polymerare preferably substantially the same along the length of the fiber. Forexample, the thickness of the one or both components is substantiallyuniform along the length or axis of the fiber. Additionally oralternatively, the volume, volume fraction, or cross-sectional surfacearea of one or both (preferably both) are substantially constant alongthe length of the fiber. Thus, the preferred bicomponent fibers of theinvention are essentially uniform along the length of the fibers.

A broad class of substantially resorbable materials suitable for thefirst component of the fibers of the present invention include naturaland synthetic substantially resorbable polymers such as those describedin the Biomedical Engineering Handbook, p. 612, (1995), which isincorporated herein by reference. Examples of these substantiallyresorbable polymers include polyglycolides, polydioxanones,polyhydroxyalkanoates, polylactides, alginates, collagens, chitosans,polyalkylene oxalate, polyanhydrides, poly(glycolide-co-trimethylenecarbonate), polyesteramides, polydepsipeptides and the like. Morespecifically, substantially resorbable polymers include polyglycolicacid and polylactic acid, and copolymers of glycolic acid with lacticacid or ε-caprolactone or trimethylene carbonate. In addition to thesepolyesters are the polyester-ethers such as poly-p-dioxanone.

Polyglycolides are particularly suitable polymers for the firstcomponent as they are resorbed at a rate that corresponds to the typicalhealing rate of the human body. However, it can be understood by one ofordinary skill in the art that selection of the preferred polymer forthe first component will depend on a number of factors, including forexample the particular application or desired function of theimplantable article or implantable fiber and the desired resorption ratefor the first component in that application. The molecular weight of thepolymer is not particularly critical. However, examples ofpolyglycolides include polymers possessing a molecular weight of atleast about 2000 daltons, for example. The ratio of glycolic acid andlactic acid in a suitable polyglycolide can also vary widely, depending,for example, on the desired rate of degradation in vivo, as is generallyknown in the art.

Most preferably, the first component is biopositive. In a firstpreferred embodiment, the first component is formed from a resorbablematerial which is itself biopositive by virtue of its composition orstructure. Examples of such polymers include certain resorbable polymerssuch as polyglycolic acid and polylactic acid, copolymers of glycolicacid with lactic acid or ε-caprolactone or trimethylene carbonate. Inaddition to these polyesters are the polyester-ethers such aspoly-p-dioxanone. In a second preferred embodiment, the first componentis formed from a resorbable material which further includes at least oneadditive which renders the first component biopositive. Such would bethe case, for example, with a polymer having incorporated therein oradded or applied thereto additives such as heparin or other materialswhich impart biopositivity.

In a preferred embodiment, the first component can also befiber-forming, as that term is normally employed in the art, under theconditions of manufacture of the fiber. In such an embodiment, the firstcomponent of the bicomponent fiber can contribute to the tenacity of thefiber and/or can be substantially or highly oriented.

The polymer used to form the second component 6 of the fiber 2 may beany known fiber-forming natural or synthetic polymer such as, forexample, a polyester, polyamide, polyolefin, polyurethane,polyester/polyether block copolymers or other composition which bringsto the final fiber desired mechanical properties, alone and/or togetherwith the first component. Particular examples of such polymers includepolypropylene, polyethylene, polybutyleneterephthalate andpolyhexyleneterephthalate and copolymers thereof. In one embodiment, thesecond component can be a polymer characterized by the ability to form afiber at a temperature of at least about 120° C., preferably, at leastabout 150° C. In another embodiment, the second component, together withthe first component, is substantially oriented. In one preferredembodiment of the invention, it has been found that bicomponent fiberscan be formed from polymers, employed as the first and/or secondcomponent, which can withstand or sustain high temperatures during fiberformation while maintaining or achieving good to superior mechanicalintegrity of the fiber.

Preferably, the polymer is not substantially resorbable; however, it isto be understood by one of ordinary skill in the art that polymers whichmeet the definition of the term resorbable material as utilized hereinmay be utilized for the second component 6 (FIGS. 1A-1C). Should aresorbable polymer be utilized in the second component 6, it ispreferred that such a polymer have a rate or resorption different than,most preferably slower than, that of the resorbable material for thefirst component.

As above, the molecular weight of the fiber-forming polymer of thesecond component is not critical to the invention. The molecular weightis generally sufficient to form a fiber in, for example, monocomponentmelt spinning. Examples of suitable polyesters can possess a molecularweight of at least about 15,000 daltons or at least about 20,000daltons. Where a polyolefin is selected, the molecular weight can be atleast about 60,000 daltons or at least about 70,000 daltons or,preferably, at least about 100,000 daltons.

In one embodiment of the invention, the second component of the fiber isa polymer possessing a melting point which is substantially the same orless than the melting point of said first component. Where the firstcomponent is a polyglycolide (such as PGA or PLGA) and the secondcomponent is a polyester, the melting point of the polyester secondcomponent can be greater than about 100° C. Likewise, where the firstcomponent is a polyglycolide and the second component is a polyolefin,the melting point of the polyolefin can be greater than about 100° C.

In an embodiment of the present invention, at least one of thecomponents 4 or 6, or both components 4 and 6, further include at leastone additional ingredient, such as a pigment or pharmaceutically activeagent, which may be, for example, applied to the fiber or componentsthereof and/or incorporated within the polymer. In a preferredembodiment of FIG. 1A, at least the first component 4 includes a pigmentor pharmaceutically active agent. The pharmaceutically active agent maybe the same as or different from an additive described above whichimparts biopositivity to the first component (such as, heparin). Theincorporation of pharmaceutically active agents may be desired toaugment the local healing response to the fiber or to provide local orsystemic delivery of agents which improve device performance andclinical outcome. For example, in the embodiment wherein the implantablearticle of the present invention is useful in vascular graftapplications, the pharmaceutically active agents could includetherapeutic targets involving coagulation events, hyperplasia andhypertrophic tissue response, downstream vascular patency and flow, andinfection. Nonvascular applications for the fiber/implantable articlecan benefit from an entirely different tissue response than vascularapplication and these could be mediated by a combination of active agentand polymer.

Particularly useful agents include:

1) thrombosis inhibitors such as: inhibitors of enzymes in the intrinsicor extrinsic coagulation cascade such as heparin, hirudin, or tickanticoagulant peptide, antiplatelet agents such as inhibitors ofglycoprotein IIb/IIIa or the prostacyclin analogs,

2) fibrinolytics such as tissue plasminogen activator, streptokinase andurokinase,

3) vasodilator substances such as prostacyclin and nitric oxide donormolecules,

4) anti-inflammatory agents such as the steroids and nonsteroidal drugs,

5) cell proliferation inhibitors such as c-myb and c-myc antisenseoligonucleotides and mitosis inhibitors,

6) inhibitors of matrix elaboration or expression such as collagenantisense nucleotides or amino acid analogs which inhibit collagengelation such as beta-aminopropionitrile or halofunginone,

7) inhibitors of cell migration such as RGD peptides or peptide orpeptidomimetic antagonists of integrins,

8) promoters of endothelial cell proliferation such as the vascularendothelial growth factors, acidic fibroblast growth factors and basicfibroblast growth factors, and

9) promoters of osteogenesis and chrondogenesis such as members of theTGFβ superfamily or members of the bone morphogenetic protein family.

It should also be understood that one or both components can includeother additives as well. For example, pigments, dyes, stabilizers,antioxidants, and/or antiozonates can be added to one or both polymercomponents. Preferably, the additive is pharmaceutically acceptable, asis known in the art. The additives can improve stability during fabricprocessing conditions and/or fiber properties in the body. It will beunderstood by one of ordinary skill in the art that the types andamounts of these additives can depend upon different factors such as thetemperatures of processing, the environmental conditions to which thefibers are exposed during fabrication into medical devices, storage andeventually upon the environment to which the fibers are exposed in thebody.

In other embodiments, natural or genetically altered cells from human orother sources are alternatively or additionally attached to orincorporated into the fiber structures to seed the implant article withcells that, upon multiplication and/or differentiation in the implant,impart desired biopositive or physiological characteristics to theimplant.

It should be understood by one of ordinary skill in the art that thenature and type of the pharmaceutically active agent should be selectedbased on the particular application/utility or desired function of theimplantable device or implantable fiber. For example, a fibrous mesh ofthis invention seeded with human allograft or autograft beta cells canbe implanted to create an artificial insulin-secreting gland followingtotal pancreatectomy. Such cells can be present alone or in combinationwith pharmaceutically active agents.

In an embodiment wherein both components 4 and 6 include apharmaceutical agent or living cells, the pharmaceutical agent or cellsof component 4 may be the same as or different from the pharmaceuticalagent of component 6. The pharmaceutical agent may be added or appliedafter the fiber is formed or may be incorporated into the polymer matrixprior to formation of fiber.

In a preferred embodiment, shown in FIG. 1A, the bicomponent fiber ofthe present invention is a single filament. In this embodiment, thefirst component 4 and second component 6 are preferably formedsimultaneously which results in several advantages such as the abilityto control the ratio of first component to second component along thelength of the fiber as well as amongst fibers in an article whichincludes such fibers.

Fibers of the present invention are preferably formed by any of severaldifferent methods generally known in the art which result in thesimultaneous formation of first component and a second component. Suchprocesses are exemplified in the references noted in the publicationBicomponent Fibers A Review of the Literature, Textile ResearchInstitute, Report No. 44, (1993) which is herein incorporated byreference. Examples of processes which can be modified to manufacturebicomponent fibers of the present invention include melt spinning,solution wet spinning and solution dry spinning, each of which will bediscussed in more detail below.

In each of the examples and processes described below, the firstcomponent is formed from a substantially resorbable material which is asubstantially biopositive, resorbable polymer and the second componentis formed from a fiber-forming polymer which is not substantiallyresorbable. Thus, the invention includes a method for manufacturing animplantable bicomponent fiber comprising simultaneously melt-extrudingfrom a spinnerette in a sheath-core filament configuration, a firstpolymer component formed from a substantially resorbable material and asecond component formed from a fiber-forming polymer.

In another embodiment, the invention includes a method for manufacturingan implantable bicomponent fiber comprising (a) simultaneouslysolution-spinning from a spinnerette in a sheath-core filamentconfiguration, a first solution comprising a first solvent and a firstpolymer component formed from a substantially resorbable material and asecond solution comprising a second solvent and a second componentformed from a fiber-forming polymer, thereby forming a prefilament and(b) removing substantially all of said first and second solvents fromsaid prefilament thereby forming a bicomponent fiber wherein said secondcomponent is substantially disposed within said first component. Inparticular, the first and second solvents are removed by extraction witha coagulation liquid or by evaporation.

FIG. 2 discloses one embodiment of a method for forming a fiber of thepresent invention as depicted in FIG. 1A via a melt spinning process. InFIG. 2, resorbable polymer 80 and fiber-forming polymer 82 are meltedand simultaneously extruded through melt extruders 84 and 86respectively. Polymers 80 and 82 are extruded through a spinnerette 88via spinning capillaries 90 to form streams which are cooled, typicallyby gaseous crossflow 91, to form fibers 92 having first components 94formed of polymer 80 and second components 96 formed of polymer 82. Themelt temperatures and extrusion conditions are dictated by severalfactors such as the melt and degradation temperatures and viscosity ofresorbable polymer 80 and fiber-forming polymer 82, and thecharacteristics of extruders 84 and 86, spinnerette 88 and spinningcapillaries 90 used to produce fiber 92 having first component 94 formedfrom a resorbable polymer and second component 96 formed from afiber-forming polymer. In a melt formation process the more commonpolymers used have melting point ranges from polyethylene (with amelting point of about 115° C.) to nylon 6,6 and polyethyleneterephthalate (with melting points of about 260° C.). A preferredpolymer pair for this process are polyglycolic acid for the resorbablematerial and polypropylene for the fiber-forming polymer.

FIG. 3 discloses one embodiment of a method of forming a fiber of thepresent invention as depicted in FIG. 1A via a solution dry spinningprocess. In FIG. 3, resorbable polymer 100 and fiber-forming polymer 102are dissolved in appropriate solvent(s) 104 and/or 106. The selection ofthe solvent depends upon the type of polymer and can differ forresorbable polymer 100 and fiber-forming polymer 102. Examples ofsolvents include water, acetone, dimethylformamide, dimethyl acetamide,methyl ethyl ketone, chloroform, methylene chloride, ethyl acetate,n-butanol and the like. The solvent/polymer mixtures 108 and 110 areextruded through spinnerette 112 and spinning capillaries 114 to formfibers 116. The solvent(s) 104 and/or 106 are generally evaporated fromthe extruded components 118 and 120 by a gaseous cross flow (e.g., hotgas) 122 (usually air or N₂). An example of a fiber that would bepreferably made by this process would be one in which the resorbablepolymer is not “meltable” such as the alginates, chitosans or amino acidpolymers. Preferred choices for the fiber-forming polymer for thisprocess would be polyesters, polyamides, polyolefins, polyurethanes orpolyester-polyether block copolymers or their chemically modified (forsolubility characteristics) derivatives.

FIG. 4 discloses one embodiment of a method of forming a fiber of thepresent invention as depicted in FIG. 1A via a solution wet spinningprocess with a wet jet. In FIG. 4, resorbable polymer 140 andfiber-forming polymer 142 are dissolved in appropriate solvent(s) 144and/or 146. The selection of the solvent depends upon the type ofpolymer and may differ for resorbable polymer 140 and fiber-formingpolymer 142. Examples of solvents include water, acetone, methyl ethylketone, dimethylformamide, dimethyl acetamide, n-butanol and the like.The solvent/polymer mixtures 148 and 150 are extruded throughspinnerette 152 and spinning capillaries 154, directly into acoagulation bath 156 which is filled with a coagulation liquid,typically a mixture of a solvent and water or any appropriatecombination of miscible or immiscible solvent(s) and non-solvent(s).This process forms fibers 158 having first components 160 formed ofresorbable polymer 140 and second components 162 formed of fiber-formingpolymer 142. An example of a fiber that would be usefully made by thisprocess would be one in which the resorbable polymer is not meltablesuch as the hyaluronic acids, their esters and deacetylated hyaluronicacid derivatives, alginates, chitosans or amino acid polymers. Preferredchoices for the fiber-forming polymer for this process would bepolyesters, polyamides, polyolefins, polyurethanes orpolyester-polyester block copolymers or their chemically modified (forsolubility characteristics) derivatives.

FIG. 5 discloses one embodiment of a method of forming a fiber of thepresent invention via a solution wet spinning process with a dry jet. InFIG. 5, resorbable polymer 180 and fiber-forming polymer 182 aredissolved in appropriate solvent(s) 184 and/or 186. The selection of thesolvent depends upon the type of polymer and may differ for resorbablepolymer 180 and fiber-forming polymer 182. Examples of solvents includeacetone, dimethylformamide, dimethyl acetamide, n-butanol and the like.The solvent/polymer mixtures 188 and 190 are extruded throughspinnerette 192 and spinning capillaries 194, through a gap 195, usuallyair, into a coagulation bath 196 which is filled with a coagulationliquid, typically a mixture of a solvent and water. This process formsfibers 198 having a first component 200 formed of resorbable polymer 180and a second component 202 formed of a fiber-forming polymer 182. Anexample of a fiber that would be usefully made by this process would beone in which the resorbable polymer is not meltable such as thehyaluronic acids, their esters and deacetylated hyaluronic acidderivatives, alginates, chitosans or aminoacids polymers. Preferredchoices for the fiber-forming polymer for this process would bepolyesters, polyamides, polyolefins, polyurethanes orpolyester-polyether block copolymers or their chemically modified (forsolubility characteristics) derivatives.

The solution formation processes shown in FIGS. 3-5 and discussed abovemay be carried out at moderate or room temperatures (15° C. to 35° C.).Room temperature (or close to room temperature) processing allows theuse of a wide variety of additives and/or drugs which might decompose ordegrade at elevated temperatures. In the solution formation processesshown in FIGS. 4 and 5, the resorbable polymer and the fiber-formingpolymer may be matched with the polymers' respective solvents. Suitablesolvents may be selected from a class of more “biofriendly” solvents, orsolvents which can be employed in the manufacture of pharmaceuticalproducts, for example water, n-butanol, tetrahydrofuran (THF),n-methylpyrrolidone (NMP) or ethylacetate, so that any trace residualsremaining within the fiber, particularly the first component of thefiber, do not adversely react with the body at that concentration.

Although it is preferable as discussed above that the first componentand the second component be simultaneously formed in this embodiment, itis to be understood that other processes that result in sequentialformation of the first and second components are within the scope of theinvention. For example, the first component may be applied as a coatingvia conventional coating processes such as dip coating (e.g., through asolution comprising the first polymer component and a suitable solvent)or plasma coating to the second component after the second component isformed via conventional filament spinning processes.

In any event, as discussed above, the process selected will dependlargely upon the properties of the first and second component (therelative melting points and degradation temperatures, the solubilities,and the presence of one or more additives, for example).

In a second embodiment, shown in FIG. 1B, the fiber of the presentinvention is a multifilament fiber wherein the second component 6includes a plurality of individual filaments 10. In this embodiment,first component 4 is preferably applied as a coating to the secondcomponent after the second component is formed via conventional filamentspinning processes.

The implantable fibers of the present invention are particularly usefulin applications relating to implantable medical articles 300,particularly sterile, implantable medical articles, such as the vasculargraft depicted in FIG. 6 which include a textile-based structure 40 asdepicted in FIG. 7. Preferred textile-based structures include aplurality of fibers with at least one of the fibers being an implantablebicomponent fiber of the present invention. Non-limiting examples oftextile-based structures include fabrics, cloths, webs or similarstructures which can have, for example, woven, knitted, braided ornon-woven constructions. Textile-based structures may contain a singlefiber of the present invention or a plurality of fibers of the presentinvention. As such, it is preferred that the fibers of the inventionpossess sufficient mechanical properties (including, for example,tensile strength, flexibility, creep and elongation properties) topermit manufacture of textiles suitable for implantation. For example,it is desirable that the fiber have sufficient tensile strength as toavoid breakage during commercial weaving and or knitting. Generally, afiber characterized by a filament diameter of about 15 microns ispreferably characterized by a tensile strength of at least about 1.5grams per denier, preferably at least about 3.5 grams per denier.Elongation is generally preferred to be less than 65% at conditions ofuse.

Textile-based structures and processes for their formation are wellknown in the art as exemplified and described in textbooks such asTextiles by N. Hollen and J. Saddler, The MacMillan Company (1973). Informing the textile structures useful in these applications, it is to beunderstood that, depending on the specific utility of the implantablearticle, the textile structure may include the fibers of the presentinvention, yarns formed from the fibers of the present invention or acombination thereof, as well as other implantable synthetic polymerfibers already known to the art. For textile-based structures whichinclude fibers of the present invention or yams formed therefrom, it ispreferred that the textile-based structure include interstices 45 (FIG.7) along the structure.

Examples of such implantable medical articles include prosthetics suchas vascular grafts, stents, artificial replacement ligaments,implantable soft tissue prostheses such as breast and penile prostheses;cartilage replacement prostheses for the joints, nose and ear;implantable support meshes; hernia implant fabrics; AV shunts;tympanoplasty patches; atrial, ventricular, septal and pericardialpatches; endarterectomy patches and the like. Other examples includesuture cuffs and tags and other exterior structures for medicalimplants, such as implantable heart valves, including artificial valvesand natural hetero- and homo-graft valves; intracranial pressure reliefvalves; implantable pacemakers and defibrillators; implantable monitorsand drug delivery pumps; and the like.

It will be understood by one of ordinary skill in the art that thefibers of the present invention should not include any material orcomponent which would induce an unacceptable toxic, cytotoxic orimmunogenic response once implanted as part of these or otherimplantable articles.

While the present invention has been described with detail and withspecific references to preferred embodiments, it is to be understoodthat many variations of the present invention which do not depart fromits spirit and scope may be made. For example, the fibers of the presentinvention may further include one or more outer coatings on the surfacethereof, including cell coatings, which may improve their implantabilityor performance. Also, the polymer utilized for the second component mayalso be a resorbable material as that term is defined and may haveresorption characteristics different from those of the resorbablematerial utilized for the first component. For example, the firstcomponent may be formed from a first resorbable material and the secondcomponent may be formed from a polymer which is a second resorbablematerial the first and second resorbable materials have differentialresorption rates. Implantable articles formed therefrom would be of atemporary nature or used in applications where their useful life isrelatively short. Further, the articles of the present invention may beused in conjunction with other implantable articles comprising otherimplantable materials, including without limitation implantablesynthetic polymers in fiber, sheet or solid structural form; metals suchas stainless steel and vitallium; and other biocompatible materials suchas ceramics, pyrolytic carbons, hydroxyapatites and the like.

EXPERIMENTAL

General Process Descriptions

1) Two Step Spin and Draw Process

Referring to FIG. 2, the core materials 82, polypropylene (PP, AristechChemical Corporation—F040A extrusion grade for sutures, nominal meltflow index of 4)) or polybutyleneterephthalate (PBT, EntecPolymers-Celanex 1600A (unfilled and low flow) and Celanex 2002-3(unfilled and medium flow), were dried to remove any residual moisture.The sheath material 80 (resorbable polymer like polyglycolic acid (PGA,Brimingham Polymers, Inc., homopolymer polyglocolic acid—inherentviscosity (measured at 30° C. in hexafluoroisopropanol) 1.54 dl/g)) wasdried under vacuum to a moisture level of below 0.005%. These materialswere fed into the extruders 84 and 86 (sheath side −¾″ single screwKillion extruder, core side −1.5″ single screw Johnson extruder) andprocessed at a temperature of 250° C. The extruders each fed through agear pump (Zenith) to control the individual flow rates of thematerials, thereby controlling the composition of the fiber (percentsheath and percent core). The molten polymer was fed into the spin headholding the spinnerette pack 88 where the formation of the sheath-corefiber 92 takes place. The spinnerettes were held at a temperatureranging between 245 and 268° C., as set forth in Table 1. The fibersformed were air quenched 91 to solidify the filaments. A non-aqueoussurface finish was applied to the fibers subsequently before being takenup by a feed roll and collected on a winder. The feed roll speedcontrolled the spin speed. This speed coupled with the individual flowrates of the sheath and core materials determined the final lineardensity of the fiber (denier) and the volume ratio of the fiber.

The spun fiber was then subjected to drawing, illustrated in FIG. 8. Thefiber 302 was taken from the bobbin 301 around a feed roll 303 andpassed through a heated chamber 304 or a block onto a draw roll 305. Thedraw roll speed was “x” times faster than the feed roll speed whichdetermined the draw ratio that the fiber was subjected to. The heatedchamber/block transferred enough heat to fiber to initiate mobility ofthe polymer chains enabling efficient orientation. The drawn fiber wasthen collected on the winder 306.

The drawn fiber was then dried for 24 hours at room temperature undervacuum and stored under vacuum until needed.

The spinning conditions for generating 25/75, 50/50 and 75/25 PGA/PP and50/50 PGA/PBT are listed below in Table 1. Clearly, a wide range of spinspeed can be used to generate these bicomponent fibers. The processtemperature varied from 245 to 268° C. Each threadline coming from thespinnerette consisted of 26 filaments. The number of threadlines can bevaried depending on the size of the pack, throughput (mass flow rate ofthe molten polymers) and the spin speed at which these fibers are woundup. The spun and drawn fiber properties for one set of spin conditionsfor these different compositions are also listed in the Table. Thedifferent fibers have been drawn at various draw ratios which weredetermined by the spun elongation. The spun elongation was determined bythe level of orientation in the fiber and can be changed by varying thespin speed and mass flow rate. Optical micrographs of the cross-sectionof some representative bicomponent fibers showed a controllable andreproducible method of making these bicomponent fibers.

TABLE 1 Item 3 7 6i 38S 9 10 15 Sheath PGA PGA PGA PGA PGA PGA PGA CorePP PP PP PBT PP PP PBT Spin Speed (mpm) 807.00 1342.00 900 948 1000 1000464 # of Threadlines 1 1 1 2 2 2 2 Process Temperature (° C.) 250.50249.5 250.6 255.6 263.5 263.9 268 Core Flow rate (gm/min) 3.73 11.052.30 7.00 8.4 4.4 9.1 Sheath Flow rate (gm/min) 5.65 5.65 9.08 7.60 1113.2 8.5 % Core (by volume) 50 75 25 50 50 35 50 % Sheath (by volume) 5025 75 50 50 65 50 Spun Denier 104 107 119 81 84 79 170 Spun Elongation(%) 232 265 237 183 199 216 373 Spun Tenacity (gm/denier) 1.69 1.99 1.572.09 1.5 2.2 1.1 Finish Content (%) 1.90 1.90 1.90 1.70 3.3 3.3 2.4 DrawTemperature (° C.) 88 88 88 120 88 88 120 Draw Ratio 2.7 2.9 2.9 2 2.042.00 3.48 Drawn Denier 39.17 36.74 45.69 41.14 43 39.83 50 DrawnElongation (%) 27.925 29.56 26.62 33.29 48 48 35 Drawn Tenacity(gm/denier) 4.457 4.701 4.704 3.5 3.63 3.28 2.75

Differential scanning calorimetry (DSC) traces of a 50/50 PGA/PP spunand drawn fiber indicated the PP melt at 168° C. and the PGA melt at217° C. The drawn fiber DSC also displayed the PP and PGA melting peaks;however, the shape of these peaks were altered. This reflectedmorphological changes in the PGA and PP materials when subjected todrawing. Drawing induced orientation of the polymer chains leading to arearrangement of the crystalline morphology of both the materials. Whenthe drawn fiber was taken up to 250° C. and cooled at 20° C./min to 50°C., there was a loss of the orientation and therefore the specificcrystalline morphology in the materials. This became apparent whencompared to the DSC trace of a quenched fiber without the orientationwhere the melting peaks were very broad compared to the sharper profilesseen for the drawn system.

The biological response of the bicomponent fibers (Items 3 and 38S), asevaluated by routine histopathologoy at various times in a ratsubcutaneous implant, were strikingly different from that of a 100%non-resorbable polymer fiber of similar dimensions. The initial responseseen during the first 7 to 10 days was typical of that seen at surgicalwound sites. Numerous blood-derived macrophages were observed clearingfibrin and coagulated blood in and around fibers. At 14 days and beyond,non-resorbing permanent polymer fibers, e.g., polypropylene andpolyester, provoked rapid formation of macrophage-derived multinucleargiant cells. These giant cells are thought to form from the fusion ofmacrophages. The giant cells persisted and grew in size in the permanentimplant with increased time of implantation. Extracellular matrixproduction and associated fibroblast infiltration occurred. Thebicomponent sheath/core fibers, however, produced an implant withequally numerous macrophages but the number of giant cells wasdiminished. At times after the sheath had been resorbed, the number ofmacrophages in and around the fibers declined. The tissue spaces betweenthe fibers filled with extracellular matrix and small blood vessels inboth permanent fibers and bicomponent sheath/core fibers, but thisresponse was significantly more robust in the sheath/core bicomponentfiber.

In addition to providing a biopositive substrate for tissue growthregeneration, the bicomponent fiber also promotes tissue ingrowth viaenhanced porosity as the sheath of the bicomponent fiber is resorbed.This porosity increase with implantation time can be modelled with theANSI/AMI-vp20 (1994) “Method for determination for water permeability”vascular-prosthesis test. The PGA sheath of bicomponent fibers woveninto plain-weave grafts was removed via graft immersion in ammoniumhydroxide at pH 11.0 (+/−0.5) and 25° C. (+/−2° C.) shaker bathtemperature for 16 hours. The graft was then dried and tested forporosity. The following data (in ml/cm²/min at 120 mm pressure) wasachieved:

TABLE 2 Porosity before Porosity after Item sheath removal sheathremoval  9 287 1742 (50% PGA sheath 50% PP core) 15 251 1674 (50% PGAsheath 50% PBT core) 10 564 3705 (65% PGA sheath 35% PP core)

2) Spin-draw Process

In a spin-draw process, the drawing step is added in line to thespinning process. FIG. 9 is a schematic of the process. The variousgodets are marked by 401 through 406. Godet 401 is the take-up godet andwill determine the spin speed. The fiber 416 is contacted with a finishstep 411 prior to being taken up by godet 401. The subsequent godets402, 403 and 404 can be varied in manner where a desired draw ratio isachieved. Godet 405 is a heated roll where a temperature of 100-150° C.can be maintained to effectively begin the relaxation process for thedrawn fibers 416. Godet 406 serves as the relax godet before the fibersare taken up on the winder 410.

Table 3 represents one specific condition from many possible variationsof generating a 50/50 PGA/PP fiber by the spin-draw process. The maindraw of ˜2.5 is obtained between G1 and G3, with the relaxationoccurring from G5 onwards. The hot roll, G5, is maintained at 130° C.The properties obtained by this process are comparable to that obtainedby the two step process.

TABLE 3 Item 8 Sheath PGA Core PP G1 (mpm) 730.00 G2 (mpm) 770.00 G3(mpm) 1808.00 G4 (mpm) 1808.00 G5 (mpm 1680.00 G6 (mpm) 1655.00 Winder(mpm) 1650.00 # of Threadlines 2 Process Temperature (° C.) 260.00 PGAFlow rate (gm/min) 9.50 Core Flow rate (gm/min) 6.10 % Core (vol) 50 %Sheath (vol) 50 Denier 38 Elongation (%) 31 Tenacity (gm/denier) 4.50Finish content (%) 3.30

Equivalents

While this invention has been particularly shown and described withreferences to preferred embodiments thereof, it will be understood bythose skilled in the art that various changes in form and details may bemade therein without departing from the spirit and scope of theinvention as defined by the appended claims. Those skilled in the artwill recognize or be able to ascertain using no more than routineexperimentation, many equivalents to the specific embodiments of theinvention described specifically herein. Such equivalents are intendedto be encompassed in the scope of the claims.

What is claimed is:
 1. An implantable medical article comprising atextile-based structure said structure comprising at least onebicomponent fiber, wherein the bicomponent fiber comprises a firstcomponent formed from a resorbable material and a second componentformed from a fiber-forming polymer which is non-resorbable, wherein themelting point of the second component is the same as or less than themelting point of the first component.
 2. An implantable medical articlecomprising a textile-based structure said structure comprising at leastone bicomponent fiber, wherein the bicomponent fiber comprises a firstpolymer component formed from a resorbable material and a secondcomponent formed from a fiber-forming polymer which is non-resorbablewherein the polymers in said first and second components are oriented.3. The implantable medical article according to claim 2, wherein thefirst and the second component of the bicomponent fiber aresimultaneously oriented during or subsequent to co-extrusion.
 4. Theimplantable medical article according to claim 3, wherein said secondcomponent is disposed within said first component.
 5. The implantablemedical article according to claim 3 wherein said second component isselected from the group consisting of polyesters, polyamides,polyolefins, and segmented polyurethanes.
 6. The implantable medicalarticle according to claim 3 wherein said second component is selectedfrom the group consisting of polypropylene, polyethylene,polybutyleneterephthalate and polyhexamethyleneterephthalate.
 7. Theimplantable medical article according to claim 3, wherein said firstcomponent induces a biopositive response in vivo.
 8. The implantablemedical article according to claim 3 wherein said first component isselected from the group consisting of polyglycolides, polydioxanones,polyhydroxyalkanoates, polylactides, alginates, chitosans, collagens,polyalkylene oxalates, polyanhydrides, poly(glycolide-co-trimethylenecarbonate), polyesteramides, and polydepsipeptides.
 9. The implantablemedical article according to claim 3 wherein said first component is apolyglycolide polymer or a polyglycolide-polylactide copolymer.
 10. Theimplantable medical article according to claim 3 wherein at least one ofsaid components further comprises at least one pharmaceutical agent. 11.The implantable medical article according to claim 3, wherein said firstcomponent is substantially free of cracks or delamination.
 12. Theimplantable medical article according to claim 3 wherein said firstcomponent possesses a substantially uniform thickness along the axis ofthe fiber.
 13. The implantable medical article according to claim 3wherein a volume ratio of said first component to said second componentis from about 1:10 to about 10:1.
 14. The implantable medical articleaccording to claim 3 wherein the first polymer component is afiber-forming polymer.
 15. The implantable medical article according toclaim 3, wherein the volume ratio of said first component to said secondcomponent is substantially the same along the length of the fiber. 16.An implantable medical article comprising a textile-based structure saidstructure comprising at least one bicomponent fiber, wherein thebicomponent fiber is manufactured by coextrusion of a first resorbablepolymer and a second fiber-forming polymer which is non-resorbable underconditions which form a bicomponent fiber wherein the secondfiber-forming polymer is continuously disposed within the first polymerat a substantially constant volume ratio of said first polymer to saidsecond polymer along the length of the bicomponent fiber.
 17. Animplantable medical article comprising a textile-based structure saidstructure comprising a bicomponent fiber produced by a processcomprising simultaneously melt-extruding from a spinnerette in asheath-core filament configuration, a first polymer component formedfrom a resorbable material and a second component formed from afiber-forming polymer which is non-resorbable.
 18. An implantablemedical article comprising a textile-based structure said structurecomprising a bicomponent fiber, wherein the bicomponent fiber comprisesa first polymer component formed from a resorbable material and a secondcomponent formed from a fiber-forming polymer which is non-resorbable,wherein said bicomponent fiber is produced by a process comprising thesteps of: (a) simultaneously solution-spinning from a spinnerette in asheath-core filament configuration, a first solution comprising a firstsolvent and the first polymer component and a second solution comprisinga second solvent and the second component, thereby forming aprefilament; and (b) removing said first and second solvents from saidprefilament thereby forming a bicomponent fiber wherein said secondcomponent is substantially disposed within said first component.